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从时间序列数据估计等位基因年龄和选择系数。

Estimating allele age and selection coefficient from time-serial data.

机构信息

Centre for Geogenetics, Natural History Museum of Denmark, University of Copenhagen, 1350 Copenhagen, Denmark.

出版信息

Genetics. 2012 Oct;192(2):599-607. doi: 10.1534/genetics.112.140939. Epub 2012 Jul 30.

Abstract

Recent advances in sequencing technologies have made available an ever-increasing amount of ancient genomic data. In particular, it is now possible to target specific single nucleotide polymorphisms in several samples at different time points. Such time-series data are also available in the context of experimental or viral evolution. Time-series data should allow for a more precise inference of population genetic parameters and to test hypotheses about the recent action of natural selection. In this manuscript, we develop a likelihood method to jointly estimate the selection coefficient and the age of an allele from time-serial data. Our method can be used for allele frequencies sampled from a single diallelic locus. The transition probabilities are calculated by approximating the standard diffusion equation of the Wright-Fisher model with a one-step process. We show that our method produces unbiased estimates. The accuracy of the method is tested via simulations. Finally, the utility of the method is illustrated with an application to several loci encoding coat color in horses, a pattern that has previously been linked with domestication. Importantly, given our ability to estimate the age of the allele, it is possible to gain traction on the important problem of distinguishing selection on new mutations from selection on standing variation. In this coat color example for instance, we estimate the age of this allele, which is found to predate domestication.

摘要

测序技术的最新进展使得越来越多的古代基因组数据得以应用。特别是,现在可以在不同的时间点针对几个样本中的特定单核苷酸多态性进行靶向研究。在实验或病毒进化的背景下也可以获得时间序列数据。时间序列数据应允许更精确地推断种群遗传参数,并检验关于自然选择近期作用的假设。在本文中,我们开发了一种似然方法,可从时间序列数据中联合估计选择系数和等位基因的年龄。我们的方法可用于从单个双等位基因座抽样的等位基因频率。通过用一步过程近似 Wright-Fisher 模型的标准扩散方程来计算转移概率。我们表明,我们的方法产生无偏估计。通过模拟测试了该方法的准确性。最后,通过应用于几个编码马毛色的基因座来说明该方法的实用性,这些基因座与驯化之前的模式有关。重要的是,鉴于我们估计等位基因年龄的能力,有可能解决从新突变选择与从现有变异选择中区分开来的重要问题。例如,在这个毛色的例子中,我们估计了这个等位基因的年龄,发现它早于驯化。

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